Impact of human myelin on the maturation and function of human monocyte-derived dendritic cells |
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| Authors: | Viktoria Gredler Susanne Ebner Kathrin Schanda Markus Forstner Thomas Berger Nikolaus Romani Markus Reindl |
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| Affiliation: | 1. Department of Anatomy I, University Hospitals of Cologne, Joseph-Stelzman-Straße, 50931 Cologne, Germany;2. Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstraße 6, 97070 Wuerzburg, Germany;3. Department of Neurology, University Hospitals of Cologne, Kerpener Str. 62, 50937 Cologne, Germany;4. Department of Neurology, University Hospitals of Wuerzburg, Josef-Schneider-Str. 11, 97080 Wuerzburg, Germany;1. Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Italy;2. Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliero-Universitaria, Arcispedale S. Anna, Ferrara, Italy;3. Neurology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliero-Universitaria, Arcispedale S. Anna, Ferrara, Italy;4. Section of Neurology, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy;5. INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy;1. Biogen, Inc., 115 Broadway, Cambridge, MA 02142, United States;2. Celgene Avilomics Research, 200 Cambridge Park Dr., Cambridge, MA 02140, United States;3. Juno Therapeutics, 307 Westlake Ave N, Suite 300; Seattle, WA 98109, United States;1. Institute of Neurology, Catholic University, Rome, Italy;2. Don Gnocchi Foundation, Milan, Italy |
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| Abstract: | Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-β1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance. |
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